The differential diagnosis of chorea

Chorea is a hyperkinetic movement disorder characterised by excessive spontaneous movements that are irregularly timed, randomly distributed and abrupt. In this article, the authors discuss the causes of chorea, particularly Huntington's disease and the genetic syndromes that may resemble it, including HDL1-3, inherited prion disease, spinocerebellar ataxias 1, 3 and 17, neuroacanthocytosis, dentatorubro-pallidoluysian atrophy (DRPLA), brain iron accumulation disorders, Wilson's disease, benign hereditary chorea, Friedreich's ataxia and mitochondrial disease. Acquired causes of chorea include vascular disease, post-infective autoimmune central nervous system disorders (PANDAS), drugs, systemic lupus erythematosus, antiphospholipid syndrome, thyrotoxicosis, AIDS, chorea gravidarum, and polycythaemia rubra vera. The authors suggest an approach to the clinical assessment of chorea, the value of investigations, including genetic tests (for which they offer a structured framework highlighting the importance of prior counselling), and finally briefly discuss symptomatic drug treatment of chorea

Clinical and genetic analysis of 29 Brazilian patients with Huntington’s disease-like phenotype

Huntington’s disease (HD) is a neurodegenerative disorder characterized by chorea, behavioral disturbances and dementia, caused by a pathological expansion of the CAG trinucleotide in the HTT gene. Several patients have been recognized with the typical HD phenotype without the expected mutation. The objective of this study was to assess the occurrence of diseases such as Huntington’s disease-like 2 (HDL2), spinocerebellar ataxia (SCA) 1, SCA2, SCA3, SCA7, dentatorubral-pallidoluysian atrophy (DRPLA) and choreaacanthocytosis (ChAc) among 29 Brazilian patients with a HD-like phenotype. In the group analyzed, we found 3 patients with HDL2 and 2 patients with ChAc. The diagnosis was not reached in 79.3% of the patients. HDL2 was the main cause of the HD-like phenotype in the group analyzed, and is attributable to the African ancestry of this population. However, the etiology of the disease remains undetermined in the majority of the HD negative patients with HD-like phenotype. Key words: Huntington’s disease, Huntington’s disease-like, chorea-acanthocytosis, Huntington’s disease-like 2

Late onset of Huntington's disease

Twenty-five patients with late-onset Huntington's disease were studied; motor impairment appeared at age 50 years or later. The average age at onset of chorea was 57.5 years, with an average age at diagnosis of 63.1 years. Approximately 25% of persons affected by Huntington's disease exhibit late onset. A preponderance of maternal transmission was noted in late-onset Huntington's disease. The clinical features resembled those of mid-life onset Huntington's disease but progressed more slowly. Neuropathological evaluation of two cases reveal less severe neuronal atrophy than for mid-life onset disease

Therapeutic decision making in autoimmune and inflammatory disorders of the central nervous system in children.

ABSTRACT Autoimmune and inflammatory disorders of the central nervous system can result in significant morbidity and mortality. Through the recognition of syndromes using diagnostic biomarkers, the clinician is now able to use immune suppressive therapies to improve outcomes. However, the therapeutic decision-making process is complex. The clinician has to balance the risk of disease, with the risk of treatment side effects. To achieve this balance, it is important to understand the natural history of disease, the risk of residual disability, the risk of relapse, and risk of a fatal outcome. It is also important to have some understanding of the pathological processes, as some of the entities have more reversible processes, whereas others have destructive processes. This review will assess the dynamic nature of this decision-making process, and compare some of the more severe diseases such as neuromyelitis optica, anti-N-methyl-D-aspartate receptor encephalitis and opsoclonus myoclonus ataxia syndrome, with disorders with more favourable outcomes such as Sydenham chorea and post-infectious cerebellar ataxia

New Aspects of Thromboangiitis obliterans (von Winiwarter-Buerger's Disease)

The existence of thromboangiitis obliterans as a clinical entity has been a matter of debate for many years. In contrast to other immunovasculitides there is no organ involvement while peripheral vessels are affected. Heavy smokers under 40 years of age have a high predisposition for the disease. The cerebral form shows relapsing brain infarctions which can be visualized in CCT while panarteriography remains negative. Apart from unspecific inflammatory signs in blood and CSF there are distinctive laboratory findings proving the autoimmunological character of von Winiwarter-Buerger's disease. In the serum anti-elastin antibodies, IgE and anticollagen antibody activity are detectable. In 3 patients the authors detected specific immunohistochemical findings in a biopsy specimen of the temporal artery. In addition to platelet-inhibiting substances corticoids in acute and azathioprine in chronic treatment becomes necessary

Oxidative stress parameters in plasma of Huntington's disease patients, asymptomatic Huntington's disease gene carriers and healthy subjects : a cross-sectional study

BACKGROUND : Animal data and postmortem studies suggest a role of oxidative stress in the Huntington's disease (HD), but in vivo human studies have been scarce. ----- AIM : To assess the presence of oxidative stress in HD patients and its occurrence relative to clinical symptoms. ----- METHODS : Oxidative stress markers were determined in plasma of HD patients (n = 19), asymptomatic HD gene carriers (with > 38 CAG repeats) (n = 11) and their respective sex and agematched healthy controls (n = 47 and n = 22) in a cross-sectional study. ----- RESULTS : With adjustment for age and sex, HD patients had higher plasma lipid peroxidation (LP) levels (ratio 1.20, 95% CI 1.09 to 1.32, p < 0.001) and lower reduced glutathione (GSH) levels (ratio 0.72, CI 0.55 to 0.94, p = 0.011) than their age and sex-matched controls. Although considerably younger, HD gene carriers did not differ from HD patients regarding LP and GSH levels, and had higher plasma LP (ratio 1.16, CI 1.02 to 1.32, p = 0.016) and lower GSH than their matched controls (ratio 0.73, CI 0.5 to 1.05). They had higher LP (ratio 1.18, CI 1.02 to 1.34, p = 0.019) and lower GSH (ratio 0.75, CI 0.51 to 1.11) than the healthy subjects matched to HD patients. ----- CONCLUSIONS : Oxidative stress is more pronounced in HD patients and asymptomatic HD gene carriers than in healthy subjects. Differences in plasma LP and GSH are in line with the brain findings in animal models of HD. Data suggest that oxidative stress occurs before the onset of the HD symptoms

Ataxia with oculomotor apraxia type 2: clinical, biological and genotype/phenotype correlation study of a cohort of 90 patients

Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive disease due to mutations in the senataxin gene, causing progressive cerebellar ataxia with peripheral neuropathy, cerebellar atrophy, occasional oculomotor apraxia and elevated alpha-feto-protein (AFP) serum level. We compiled a series of 67 previously reported and 58 novel ataxic patients who underwent senataxin gene sequencing because of suspected AOA2. An AOA2 diagnosis was established for 90 patients, originating from 15 countries worldwide, and 25 new senataxin gene mutations were found. In patients with AOA2, median AFP serum level was 31.0 mu g/l at diagnosis, which was higher than the median AFP level of AOA2 negative patients: 13.8 mu g/l, P = 0.0004; itself higher than the normal level (3.4 mu g/l, range from 0.5 to 17.2 mu g/l) because elevated AFP was one of the possible selection criteria. Polyneuropathy was found in 97.5% of AOA2 patients, cerebellar atrophy in 96%, occasional oculomotor apraxia in 51%, pyramidal signs in 20.5%, head tremor in 14%, dystonia in 13.5%, strabismus in 12.3% and chorea in 9.5%. No patient was lacking both peripheral neuropathy and cerebellar atrophy. The age at onset and presence of occasional oculomotor apraxia were negatively correlated to the progression rate of the disease (P = 0.03 and P = 0.009, respectively), whereas strabismus was positively correlated to the progression rate (P = 0.03). An increased AFP level as well as cerebellar atrophy seem to be stable in the course of the disease and to occur mostly at or before the onset of the disease. One of the two patients with a normal AFP level at diagnosis had high AFP levels 4 years later, while the other had borderline levels. The probability of missing AOA2 diagnosis, in case of sequencing senataxin gene only in non-Friedreich ataxia non-ataxia-telangiectasia ataxic patients with AFP level >= 7 mu g/l, is 0.23% and the probability for a non-Friedreich ataxia non-ataxia-telangiectasia ataxic patient to be affected with AOA2 with AFP levels >= 7 mu g/l is 46%. Therefore, selection of patients with an AFP level above 7 mu g/l for senataxin gene sequencing is a good strategy for AOA2 diagnosis. Pyramidal signs and dystonia were more frequent and disease was less severe with missense mutations in the helicase domain of senataxin gene than with missense mutations out of helicase domain and deletion and nonsense mutations (P = 0.001, P = 0.008 and P = 0.01, respectively). The lack of pyramidal signs in most patients may be explained by masking due to severe motor neuropathy